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Timely percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) is a cornerstone of therapy. Several analyses have demonstrated worse outcomes for patients presenting with STEMI during off-hours compared with during the workday (1). The etiology of this difference is likely multifactorial, including changes in staffing, delays in intervention, and higher procedural complications (2). Most available data derive from registries with retrospective collection of clinical characteristics and outcomes, whereas few data are available from randomized, controlled trials (1,3). There continues to be debate regarding whether this effect exists in the contemporary era (1–3). Finally, comprehensive delineation of relevant outcomes, including stent thrombosis, is rarely available from registry data. Such information is crucial to understanding differences in care. We sought to determine whether such differences existed in a large, contemporary, international trial.

We dichotomized the subgroup of patients with recent STEMI from CHAMPION PHOENIX (Clinical Trial Comparing Cangrelor to Clopidogrel Standard of Care Therapy in Subjects Who Require Percutaneous Coronary Intervention) according to time of presentation (4). Off-hour PCI was defined by intervention performed during weekdays from 7 pm to 7 am, weekends, and holidays. Continuous data are presented as mean ± SD. Categorical variables are presented as a count and percentage. Endpoints were evaluated at 48 h and 30 days. The primary efficacy outcome was a combined endpoint of all-cause death, myocardial infarction, stent thrombosis, or ischemia-driven revascularization at 48 h. The primary safety outcome for this analysis was GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries)–defined moderate or severe bleeding, whereas ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy)–defined major or minor bleeding was also examined.

Student t tests were used to compare normally distributed continuous variables (or nonparametric equivalent when appropriate). Chi-square tests (or Fisher exact tests when appropriate) were used to compare categorical variables. Because timing of PCI was not randomized, we used logistic multivariate regression with propensity score analysis to determine the risk of all outcomes. Propensity scores were constructed using age, randomization arm, enrollment site (United States vs. non–United States), previous myocardial infarction, previous PCI, history of diabetes, clopidogrel loading dose, type of anticoagulant agent, and type of stent. All study participants provided written informed consent. A 2-sided p value <0.05 was considered statistically significant.

In the STEMI cohort of CHAMPION PHOENIX (1,992 of 10,942), the mean age was 61 ± 12 years, 26% of the participants were female, and 10% were enrolled from the United States (Table 1). Most participants underwent angiography through femoral access (79%). On-hours participants were more likely to be enrolled from the United States, have diabetes mellitus, have previous PCI, and receive a higher-dose clopidogrel load, low-molecular-weight heparin, bivalirudin, and a drug-eluting stent (p < 0.05 for all comparisons). Bailout therapy with glycoprotein IIb/IIIa inhibitors was similar in the groups. Off-hours participants underwent PCI more rapidly from symptom onset (median 5.00 h vs. 5.98 h; p < 0.0001). Likewise, time from admission to PCI was also shorter for off-hours participants (median 76.8 min vs. 79.8 min; p < 0.0001).

Baseline Demographic and Clinical Characteristics According to Time of Presentation

The risk of the primary efficacy outcome was not significantly different for on-hours presentation on unadjusted analysis (OR: 1.11; 95% CI: 0.68 to 1.83; p = 0.67) or after multivariate propensity score adjustment (OR: 1.00; 95% CI: 0.57 to 1.74; p = 0.99). There was no significant difference in risk of stent thrombosis with on-hours PCI (adjusted OR: 0.57; 95% CI: 0.27 to 1.21; p = 0.15) or in the primary safety outcome (p = 0.22). Cangrelor showed consistent benefits regardless of time of PCI for all outcomes (p > 0.05 for interaction). Additionally, no interaction was observed by site of enrollment (p > 0.05 for all outcomes).

In this randomized trial, we showed that in contrast to findings from several previous studies, time of PCI did not affect STEMI efficacy or safety outcomes. These findings are reassuring and suggest that outcomes for STEMI revascularization do not depend on time of presentation. Such information is important given that previous studies suggesting a difference in efficacy were retrospective with unadjudicated outcomes. The additional collection of stent thrombosis and ischemia-driven revascularization data provides important endpoints in PCI that are not widely available in previous studies.

The present study question was not pre-specified and thus was not specifically powered for these analyses. As such, we caution interpretation and cannot rule out potential harm associated with off-hours presentation. Moreover, because CHAMPION PHOENIX was not a primary STEMI trial, door-to-balloon time was not specifically collected. Therefore, time from admission to PCI is presented; this acknowledges the potential heterogeneity of defining admission time in the trial. Additionally, although several clinical characteristics of our participants were similar to those observed in large registries, there was a lower rate of previous coronary procedures, and therefore the studied population may be at lower risk (3,5). Finally, because the times to treatment were shorter for off-hours participants, the similar efficacy and safety outcomes findings observed in this clinical trial may not apply to all STEMI programs.

In conclusion, previous hazards identified with off-hours presentation in STEMI were not seen in a large, international, contemporary trial with prospective data collection and adjudication of outcomes. Such data are reassuring and may reflect global quality improvement measures in STEMI care.

Footnotes

Please note: CHAMPION PHOENIX was sponsored by The Medicines Company. Dr. Bhatt is on the advisory boards of Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, Regado Biosciences; is on the Board of Directors of Boston VA Research Institute, Society of Cardiovascular Patient Care; is the Chair of the American Heart Association Quality Oversight Committee and the VA CART Research and Publications Committee; is on the data monitoring committees of Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, Population Health Research Institute; has received honoraria from the American College of Cardiology (Senior Associate Editor, Clinical Trials and News;acc.org), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), Population Health Research Institute (clinical trial steering committee), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees); is the Deputy Editor of Clinical Cardiology; is the Vice-Chair of the NCDR-ACTION Registry Steering Committee; has received research funding from Amarin, Amgen, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Forest Laboratories, Ischemix, Medtronic, Pfizer, Roche, Sanofi, The Medicines Company (including for his role as co-chair of the CHAMPION trials); has received royalties from Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); is a site co-investigator for Biotronik, Boston Scientific, and St. Jude Medical; is a trustee of the American College of Cardiology; and has performed unfunded research for FlowCo, PLx Pharma, and Takeda. Dr. Gibson has received research support from The Medicines Company. Dr. Steg has received research grants from Merck, Sanofi, and Servier; and has received speaking or consulting fees from Amarin, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, CSL-Behring, Daiichi-Sankyo, GlaxoSmithKline, Janssen, Lilly, Merck Novartis, Pfizer, Regeneron, Sanofi, Servier, and The Medicines Company. Dr. Hamm has received speaker’s fees and is on the advisory boards of AstraZeneca, Lilly, and Daiichi-Sankyo. Dr. Price has received consulting fees and honoraria from ACIST Medical, AstraZeneca, Boston Scientific, The Medicines Company, Medtronic, and St. Jude Medical; and speaker fees and honoraria from AstraZeneca, Abbott Vascular, The Medicines Company, and St. Jude Medical. Drs. Deliargyris and Prats are employees of The Medicines Company. Dr. Mahaffey has received research funding from Amgen, Daiichi, Johnson & Johnson, Medtronic, Merck, St. Jude Medical, and Tenax; has received consultant Fees from American College of Cardiology, AstraZeneca, BAROnova, Bayer, Boehringer-Ingelheim, Bio2 Medical, Bristol-Myers Squibb, Cubist, Eli Lilly, Elsevier, Epson, Forest, GlaxoSmithKline, Johnson & Johnson, Medtronic, Merck, Mt. Sinai, Myokardia, Omthera, Portola, Purdue, Springer Publishing, The Medicines Company, Theravance, Vindico, and WebMD; and has stock in BioPrint Fitness. Dr. White has received honoraria from AstraZeneca; and has received research funding from Sanofi, Eli Lilly, National Health Institute, GlaxoSmithKline, Merck Sharp & Dohme, AstraZeneca, Omthera Pharmaceuticals, Pfizer New Zealand, Intarcia Therapeutics, Elsai Inc, DalGen Products and Services, and Daiichi Sankyo Pharma Development. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. A full list of the CHAMPION PHOENIX Investigators can be found in Bhatt DL, Stone GW, Mahaffey KW, et al. Effect of platelet inhibition with cangrelor during PCI on ischemic events. N Engl J Med 2013;368:1303–13. The authors thank Steven E. Elkin, MS, and Debra Bernstein, PhD, of The Medicines Company for their statistical support, along with Yuyin Liu, MS, of the Harvard Clinical Research Institute for independent verification of the analyses. The Harvard Clinical Research Institute received funding from The Medicines Company for these analyses.

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